SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME QUINOXALINE DERIVATIVES AS CHOLINESTERASE INHIBITORS


Uysal Ş. , Soyer Z. , Parlar S. , Alptüzün V.

2nd International Gazi Pharma Symposium Series (GPSS) 2017, Ankara, Türkiye, 11 - 13 Ekim 2017, ss.268

  • Basıldığı Şehir: Ankara
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayısı: ss.268

Özet

Alzheimer’s disease (AD) is the most common age related neurodegenerative disease, characterized by memory loss and cognitive impairments [1]. Although the etiology of AD is not fully understood several factors, such as low levels of neurotransmitter acetylcholine, the aggregation of β-amyloid peptide, hyperphosphorylation of tau protein, and oxidative stress are considered to play important role in the pathophysiology of AD [2]. Inhibition of acetylcholinesterase (AChE), is currently the main pharmacological strategy for Alzheimer’s disease [3]. At present, AChE inhibitors have successfully reached the market such as tacrine, donepezil, rivastigmine and galanthamine, but their efficacy is limited due to peripheral adverse effects [4]. Therefore, there is an urgent need to discover and develop new agents with enhanced activity profile. Quinoxaline derivatives are an important class of heterocyclic compounds which exhibit various biological activities such as antibacterial, anti-inflammatory, anticancer , antitubercular, antileishmanial, antimalarial, antidepressant and anticholinesterase activities [5]. In this work, five compounds with quinoxaline core have been synthesized to evaluate their cholinesterase inhibitory activities compared to rivastigmine as reference compound by using Ellman’s method (Figure 1) [6]. Structure of the compounds were confirmed by spectral analysis. According to the data, all compounds displayed higher AChE inhibitory activity than BuChE inhibitory activity. Among the tested compounds, compound 3 was found to be the most active derivative against AChE with IC50 value of 7.19±0.17 µM.